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Page 2 of 6 Hu et al. Hepatoma Res 2019;5:29 I http://dx.doi.org/10.20517/2394-5079.2019.23

There may be two possible modes of HBV carcinogenesis: one is viral oncogene mode, that is, after the body
is infected with HBV, HBV will integrate into the host genome by incorporating its own genes into the
[2-4]
nucleus of hepatic cells, thus transforming normal hepatic cells into cancer cells ; the other is the cellular
oncogene mode, that is, viral DNA will integrate into or rearranges with DNA of its host to produce HBV-
activated genes or proto-oncogenes, leading to the transformation of normal cells into cancer cells and
ultimately the development of HCC .
[5,6]
It is not impossible to prevent HCC. If we can take intervention measures at the stage of CHB to prevent
the disease progression to a great extent, it is impossible to prevent a considerable number of patients with
CHB from developing into LC or even HCC. This article will focus on the secondary prevention of HBV-
related HCC-early detection, early diagnosis, standard antiviral treatment, and whole-course management
- to show its importance and clinical significance.

Screening of high-risk groups of HBV-associated HCC is helpful for early detection and diagnosis. Currently,
it is known that the high risk factors closely lead to the progression of HCC in patients with CHB mainly
include: hepatitis B e antigen (HBeAg) positive, genotype C HBV, high HBV DNA load, long-term intake of
a lot of alcohol, people with LC basis and a family history of HCC, especially men over 40 years old and so
on. Regular physical examinations should be carried out in high risk population. Regular examination of
liver function, HBV serological tests, HBV-DNA load, AFP, abdominal ultrasound, and non-invasive liver
fibrosis detection and the like every three to six months, enhanced CT test or nuclear magnetic resonance
(MRI) should be further examined in suspected patients, in order to detect small HCC early. Early surgical
resection and other radical treatment can improve the cure rate of HCC and prolong the life cycle of patients
as far as possible.

Standard antiviral treatment plays a crucial role in secondary prevention of HBV-associated HCC. In
patients with CHB, antiviral treatment has been shown to prevent disease progression to LC and HCC [7-11] .
A retrospective cohort study showed that after 5 years of follow-up, the cumulative incidence of HCC in
[12]
nucleotide analogue (NUCs) antiviral treatment group and control group (without treatment) was 3.7%-13.7%,
while the cumulative incidence of HCC was 7%-38.9% in these two groups of HBV-related LC (HBLC) patients,
indicating a long-term of antiviral treatment can reduce the risk of HCC significantly. Similar studies also
suggested that long-term NUCs treatment was associated with 77% reduction of HCC risk in LC patients.
[13]
Our team has been working on a cohort study of long-term standardized antiviral treatment and whole-course
management for patients with CHB. Our previous studies showed that compared with the control groups,
[14]
the cumulative incidence of LC in CHB patients treated with NUCs for 3-5 years was 1.4% vs. 10.2% and 2.7%
vs. 22.4%, respectively (P < 0.001), the cumulative incidence of HCC in 3-5 years was 0.2% vs. 2.3% and 0.9%
vs. 3.4%, respectively (P = 0.017) [Figure 1]. All the results mentioned above illustrated that long-term and
standard antiviral treatment can significantly reduce the risk of LC and HCC in patients with CHB.

Thus, a whole course management should be conducted in patients with high risk of HCC starting from the
discovery of HBsAg positive, including chronic HBV carriers, non-active HBsAg carriers, HBeAg-positive
and negative CHB patients, and HBLC patients in compensated and decompensated periods. As for the
chronic HBV carriers and non-active HBsAg carriers, blood routine, biochemistry, HBV serological tests,
AFP and the like should be monitored every 3 months, abdominal ultrasound, computed tomography (CT)
or non-invasive liver fibrosis detection should be carried out every 6 months, and liver biopsy should be
conducted if it is necessary. If antiviral treatment indications are met, treatment should be started in time.
For HBeAg-positive CHB patients, after 3-6 months of observation, antiviral treatment could be started if
alanine aminotransferase level continued to rise and there was no spontaneous HBeAg serological conversion.
On the contrary, for HBeAg-negative CHB patients, antiviral treatment should be started as soon as possible
if they meet the indication. For patients with HBLC, antiviral treatment should be initiated immediately
[Figure 2]. After starting antiviral treatment, patients should be followed up regularly by telephone, text